The cutaneous lymphocyte‐associated antigen (CLA) represents the homing receptor involved in selective migration of memory/effector T cells to the skin. Numerous reports demonstrated distinct CLA expression on Th1 cells. However, T cells isolated from skin lesions and CLA+ T cells circulating in peripheral blood of atopic dermatitis patients expressed high IL‐5 and IL‐13. Accordingly, we investigated the regulation of CLA on human type 1 and type 2 T cells. CLA was induced on freshly generated Th1 and Tc1 cells only, but not on those of type 2. Anti‐CD3 stimulation was sufficient to induce CLA on Th2 cells in the absence of serum in the culture medium. In serum containing medium, IL‐4 inhibited CLA and related α‐fucosyltransferase mRNA expression. IL‐12 and/or staphylococcal enterotoxin B (SEB) stimulation up‐regulated CLA expression on either Th2 and Tc2 cells. On stimulation with IL‐12, CLA was expressed on the surface of bee venom phospholipase A2‐specific Th1, Th2, Th0 and T regulatory 1 clones, representing non‐skin‐related antigen‐specific T cells. In addition, CLA could be re‐induced on T cells that had lost CLA expression upon resting. These results suggest that skin‐selective homing is not restricted to functional and phenotypic T cell subsets.

Rap1-GAP protein has been identified as an inactivator of Rap1 activity, a putative endogenous antagonist of Ras proteins. The Rap1-GA1 locus maps to 1p36.1-35, the region which may harbor a gene for familial melanoma. In the present immunohistochemical study we analyzed the clinicopathological and prognostic relevance of Rap1-GAP expression in 60 benign and 103 malignant melanocytic tumors. Cytoplasmic immunoreactivity was detected in the cells of 27/60 nevi (45%) and 59/103 melanomas (57%). In the latter group the frequency of Rap1-GAP expression increased (P < 0.05) with the thickness of primary tumors and was highest in metastatic lesions. Rap1-GAP protein was detected in 15/19 subsequently recurring primary melanomas (79%) but only in 32/67 tumors (47%) of patients who remained free of disease (P < 0.05) for at least 6 years. Five out of six recurring thin melanomas (< 2 mm) were found to be immunoreactive. Although being no indicator for malignant transformation of melanocytic lesions, Rap1-GAP overexpression may represent a useful marker for identifying thin high-risk melanomas. Cytoplasmic expression of Rap1-GAP has also been observed in the cells of skin appendages and in keratinocytes, particularly in suprabasal layers of the epidermis. Therefore, Rap1-GAP is likely to be associated with cellular growth and/or differentiation. However, the present study did not provide evidence that this gene, despite its chromosomal localization, represents an early melanoma gene.